Ilaria Notaristefano

Pediatric neurological disorders comprise a highly heterogeneous group of conditions that together represent a substantial global public health burden. Many have a strong genetic basis and are associated with significant morbidity, premature mortality, and long-term disability, with far-reaching consequences for affected children, their families, and healthcare systems worldwide. Clinical heterogeneity is a hallmark of these disorders, as pathogenic variants in the same gene can give rise to diverse phenotypes with variable severity, age at onset, and disease course. In children, ongoing brain development and somatic growth further complicate diagnosis, often leading to nonspecific or atypical presentations that differ from classical adult neurological phenotypes. Advances in genetics and genomics have fundamentally transformed the understanding, diagnosis, and classification of pediatric neurological diseases. The widespread use of high-throughput sequencing, genome-wide association studies, and integrative bioinformatics approaches has enabled the rapid and precise identification of disease-associated genes, even in sporadic and complex conditions, facilitating earlier and more accurate diagnoses and highlighting the role of genetic background and gene–environment interactions in disease pathogenesis. Here we provide an overview of the genetic and genomic landscape of key pediatric neurological disorders with well-characterized molecular etiologies, including neuromuscular disorders, epilepsies, neurodevelopmental disorders, neurodegenerative diseases, and movement disorders. Current knowledge is synthesized with emphasis on clinical presentation, genetic architecture, and genotype–phenotype correlations. Gene-specific management strategies and emerging precision therapies are discussed for selected conditions, underscoring the central role of genetic diagnosis in guiding clinical decision-making and improving outcomes in affected children.

Background: Moral development (MD) arises from the interaction of attachment, temperament, emotion regulation, and decision-making. Children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) frequently show impairments across these domains, suggesting increased vulnerability to disruptions in MD. However, the mechanisms linking ADHD to MD remain poorly understood. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed was searched for studies published between January 2014 and November 2024 examining MD-related constructs, including moral reasoning, fairness, aggression, bullying, callous–unemotional (CU) traits, decision-making, and reward sensitivity, in individuals aged 0–18 years with diagnosed or subclinical ADHD. Due to substantial heterogeneity in study design, measures, and outcomes, a qualitative synthesis was performed. Results: Of the 2104 records identified, 23 studies met inclusion criteria. Insecure or disorganized attachment, difficult temperament, and emotional dysregulation consistently emerged as developmental risk factors for impaired MD. Hyperactivity–impulsivity and deficient inhibitory control were strongly associated with aggressive and antisocial behaviors. Children with ADHD demonstrated a pronounced preference for immediate over delayed rewards, altered decision-making in social contexts, and reduced sensitivity to positive feedback. CU traits and aggression were frequently identified as behavioral correlates of MD impairments, particularly in interaction with family adversity and comorbid externalizing conditions. Social dysfunction, including bullying involvement, peer rejection, and interpersonal difficulties, was common and contributed to elevated long-term psychosocial risk. Conclusions: ADHD is associated with multidimensional vulnerabilities in MD through intertwined cognitive, emotional, and relational pathways. Interventions targeting attachment security, emotion regulation, reward processing, and social skills may foster MD and reduce later social difficulties. Longitudinal and cross-cultural research is needed to clarify causal mechanisms and inform developmentally sensitive prevention and treatment strategies.

Background Autoimmune encephalitis (AE) comprises a rare and heterogeneous group of immune-mediated disorders affecting the central nervous system, frequently characterized by both psychiatric and neurological symptoms. In pediatric populations, acute psychiatric manifestations, such as agitation, mood instability, and psychosis, may precede neurological signs, often complicating early diagnosis due to their overlap with primary psychiatric disorders. This retrospective observational study aimed to characterize the early psychiatric presentations of pediatric AE through the analysis of clinical records concerning inpatient admissions to a tertiary Child and Adolescent Neuropsychiatry Unit. Materials and Methods We screened 1,577 inpatient admissions for cases presenting with acute-onset psychiatric symptoms (July 2022–July 2024). Of 58 patients, 6 (mean age: 10.3 ± 5.2 years; 4 males, 2 females) received a final diagnosis of definite or probable AE based on established pediatric guidelines, thus meeting our inclusion criteria. Results All patients presented with psychiatric symptoms, including externalizing behaviors (2/6), mood disturbances with psychotic features (4/6), and sleep disorders (4/6). All underwent comprehensive diagnostic evaluations, including cerebrospinal fluid (CSF) analysis, electroencephalography, and brain MRI. CSF biochemical abnormalities were detected in 5 out of 6 patients, while neuronal antibodies were identified in 4 out of 6 cases (two with anti-NMDAR and two with anti-GAD65 positivity, including one with both). Conclusions Our findings underscore the relevance of early psychiatric symptoms in pediatric AE and emphasize the importance of considering autoimmune etiologies in new-onset psychiatric presentations, particularly in the absence of prior psychiatric history.